公开(公告)号：US06849723B2

公开(公告)日：2005-02-01

申请号：US10195211

申请日：2002-07-15

申请人： Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

发明人： Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

IPC分类号： C07H21/00 ,  C12N15/113 ,  C12Q1/68 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1135 ,  C07H21/00 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12Q1/6876 ,  Y02P20/582 ,  C12N2310/3525

摘要： Modified dimers having a ribose sugar moiety in the 5′ nucleoside and a 2′ modified sugar in the 3′ nucleoside are provided. The modified dimers are useful in the preparation of oligonucleotide analogs having enhanced properties compared to native oligonucleotides, including increased nuclease resistance, enhanced binding affinity and improved protein binding.

摘要翻译： 提供了在5'核苷中具有核糖部分和3'核苷中的2'修饰的糖的修饰二聚体。 修饰的二聚体可用于制备与天然寡核苷酸相比具有增强的性质的寡核苷酸类似物，包括增加的核酸酶抗性，增强的结合亲和力和改善的蛋白质结合。

公开(公告)号：US06528631B1

公开(公告)日：2003-03-04

申请号：US09098166

申请日：1998-06-16

申请人： Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

发明人： Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

IPC分类号： C07H2102

CPC分类号： C12N15/113 ,  A61K47/51 ,  C07H21/00 ,  C12N15/1131 ,  C12N15/1132 ,  C12N15/1133 ,  C12N15/1135 ,  C12N15/1138 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/3527

摘要： Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2′-, 3′-, 5′-, nucleobase and internucleotide linkage sites. The folate can be attached via the &agr;- or &ggr;-carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are disclosed.

摘要翻译： 描述了寡核苷酸 - 叶酸盐缀合物，其中叶酸酯与包含2'，3'，5'，核碱基和核苷酸间位点的寡核苷酸上的一个或多个位点缀合。 叶酸可以通过α-或γ-羧酸盐，任选地通过连接基团连接。 公开了区域特异性合成缀合物的方法。

公开(公告)号：US06335434B1

公开(公告)日：2002-01-01

申请号：US09275505

申请日：1999-03-24

申请人： Andrei P. Guzaev ,  Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

发明人： Andrei P. Guzaev ,  Phillip Dan Cook ,  Muthiah Manoharan ,  Balkrishen Bhat

IPC分类号： C12Q168

CPC分类号： C07H15/26 ,  C07D475/04

摘要： Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2′-, 3′-, 5′-, nucleobase and internucleotide linkage sites. The folate can be attached via the &agr;- or &ggr;-carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are diclosed. Also disclosed are nucleosidic and non-nucleosidic linkers conjugated to folic acid and related folates.

摘要翻译： 描述了寡核苷酸 - 叶酸盐缀合物，其中叶酸酯与包含2'，3'，5'，核碱基和核苷酸间位点的寡核苷酸上的一个或多个位点缀合。 叶酸可以通过α-或γ-羧酸盐，任选地通过连接基团连接。 缀合物区域特异性合成的方法是分开的。 还公开了与叶酸和相关叶酸缀合的核苷和非核苷酸接头。

公开(公告)号：US09127272B2

公开(公告)日：2015-09-08

申请号：US13353114

申请日：2012-01-18

申请人： Christine Esau ,  Eric E. Swayze ,  Balkrishen Bhat ,  Garth A. Kinberger

发明人： Christine Esau ,  Eric E. Swayze ,  Balkrishen Bhat ,  Garth A. Kinberger

IPC分类号： C12N15/113 ,  C12N15/11

CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/51 ,  C12N2310/3527 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activing in a cell.

摘要翻译： 提供化合物，组合物和方法用于调节miRNA的水平表达，加工和功能。 组合物包含靶向小的非编码RNA和miRNA的寡聚化合物。 寡聚化合物具有有效的miRNA抑制活性，并进一步表现出改善的治疗指数。 还提供了选择性调节细胞中miRNA活化的方法。

公开(公告)号：US20140107183A1

公开(公告)日：2014-04-17

申请号：US14111976

申请日：2012-04-25

申请人： Balkrishen Bhat

发明人： Balkrishen Bhat

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/3231 ,  C12N2310/343 ,  C12N2310/35

摘要： Described herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modification patterns that yield potent inhibitors of miR-21 activity. The compositions may be used to inhibit miR-21, and also to treat diseases associated with abnormal expression of miR-21, such as fibrosis and cancer.

公开(公告)号：US08604183B2

公开(公告)日：2013-12-10

申请号：US10701007

申请日：2003-11-04

申请人： Charles Allerson ,  Balkrishen Bhat ,  Anne B. Eldrup ,  Muthiah Manoharan ,  Richard H. Griffey ,  Brenda F. Baker ,  Eric E. Swayze

发明人： Charles Allerson ,  Balkrishen Bhat ,  Anne B. Eldrup ,  Muthiah Manoharan ,  Richard H. Griffey ,  Brenda F. Baker ,  Eric E. Swayze

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68 ,  C12P19/34

CPC分类号： C07H21/00 ,  C07H21/04 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/343 ,  C12N2310/3521 ,  C12N2310/3533 ,  C12N2320/51

摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

公开(公告)号：US20120157514A1

公开(公告)日：2012-06-21

申请号：US13412307

申请日：2012-03-05

申请人： Christine Esau ,  Bridget Lollo ,  C. Frank Bennett ,  Susan M. Freier ,  Richard H. Griffey ,  Brenda F. Baker ,  Timothy A. Vickers ,  Eric G. Marcusson ,  Erich Koller ,  Eric E. Swayze ,  Ravi Jain ,  Balkrishen Bhat ,  Eigen Peralta

发明人： Christine Esau ,  Bridget Lollo ,  C. Frank Bennett ,  Susan M. Freier ,  Richard H. Griffey ,  Brenda F. Baker ,  Timothy A. Vickers ,  Eric G. Marcusson ,  Erich Koller ,  Eric E. Swayze ,  Ravi Jain ,  Balkrishen Bhat ,  Eigen Peralta

IPC分类号： A61K31/712 ,  C12Q1/68 ,  A61P37/00 ,  C12N5/07

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/3181 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/11 ,  C12N2320/30 ,  C12N2320/50 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

公开(公告)号：US20100190837A1

公开(公告)日：2010-07-29

申请号：US12527417

申请日：2008-02-15

申请人： Michael T. Migawa ,  Eric E. Swayze ,  Balkrishen Bhat

发明人： Michael T. Migawa ,  Eric E. Swayze ,  Balkrishen Bhat

IPC分类号： C07H19/06 ,  C07H21/00 ,  A61K31/7088 ,  C12N5/00

CPC分类号： C07H19/06 ,  C07H19/16 ,  C07H21/00 ,  C12N15/111 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/319 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2320/51 ,  C12N2310/3525

摘要： The present invention provides 5′-substituted-2′-F nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In one preferred embodiment the nucleoside analogs have either (R) or (5)-chirality at the 5′-position. These nucleoside analogs are expected to be useful for enhancing properties of oligomeric compounds including nuclease resistance.

摘要翻译： 本发明提供了包含这些核苷类似物的5'-取代-2'-F核苷类似物和低聚化合物。 在一个优选的实施方案中，核苷类似物在5'-位具有（R）或（5） - 亲代性。 预期这些核苷类似物可用于增强包括核酸酶抗性的寡聚化合物的性质。

公开(公告)号：US20100184966A1

公开(公告)日：2010-07-22

申请号：US12751706

申请日：2010-03-31

申请人： Punit P. Seth ,  Eric E. Swayze ,  Balkrishen Bhat

发明人： Punit P. Seth ,  Eric E. Swayze ,  Balkrishen Bhat

IPC分类号： C07H21/04

CPC分类号： C07H19/04 ,  C07H21/00

摘要： The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

摘要翻译： 本发明提供了包含这些核苷类似物中的至少一种的5'-修饰的双环核苷类似物和寡聚化合物。 在优选的实施方案中，核苷类似物在5'-碳上具有（R）或（S） - 亲和性。 这些双环核苷类似物可用于增强低聚化合物的性质，包括例如增强的核酸酶抗性。

公开(公告)号：US20100093836A1

公开(公告)日：2010-04-15

申请号：US12524778

申请日：2008-01-29

申请人： Balkrishen Bhat ,  Eric E. Swayze ,  Walter F. Lima ,  Stanley T. Crooke

发明人： Balkrishen Bhat ,  Eric E. Swayze ,  Walter F. Lima ,  Stanley T. Crooke

IPC分类号： A61K31/7088 ,  C07H19/04 ,  C12N5/02

CPC分类号： C07H21/00 ,  C12N15/113 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2310/3533

摘要： The present invention includes compositions and methods useful for modulating protein expression. In certain embodiments, the present invention includes oligomeric compounds comprising modified nucleosides and modified internucleoside linkages.

摘要翻译： 本发明包括可用于调节蛋白质表达的组合物和方法。 在某些实施方案中，本发明包括包含修饰的核苷和经修饰的核苷间键的寡聚化合物。